This K01 award facilitates the attainment of the Candidate's long-term goal of contributing to the science base that will inform future regulatory policy on nicotine content in cigarettes, particularly as this policy affects adolescents. The activities outlined in this application afford the Candidate excellent training in youth smoking, human behavioral pharmacology and advanced statistical methods; and the Candidate proposes applying this knowledge to an innovative research plan focused on evaluating very low nicotine content cigarettes in adolescent smokers. Reducing the nicotine content of cigarettes to a non-addictive level - a strategy made possible by the 2009 passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) - could dramatically reduce smoking rates in the US (Benowitz & Henningfield, 1994). The legislation has the potential to impact the pattern of cigarette smoking over the lifetime, making cigarettes less reinforcing for young people, and thus decreasing the number of teen chippers who go on to be lifelong smokers (Sofuoglu & LeSage, 2012). However, little is known about the effects of very low nicotine content (VLNC) cigarettes in adolescents. The optimal dose of nicotine for reducing cigarette demand, effects on smoking topography, acceptability of these cigarettes and adolescents' perceptions of the relative risks of these cigarettes are all open questions. While an FDA-mandated reduction in the nicotine content of cigarettes has the potential to dramatically reduce smoking rates in the population, reducing the nicotine content of cigarettes could have unintended negative consequences in adolescents if these smokers engage in compensatory smoking or perceive VLNC cigarettes as being low in harm. Therefore, evaluating the positive and negative consequences of VLNC cigarette use among adolescent smokers is critical for evaluating the viability of this policy. We propose to examine the effects of VLNC cigarettes using two studies, one completed in the laboratory and one in the natural environment. In Study 1, we will compare the effects of cigarettes varying in nicotine content (normal nicotine content, 0.83], reduced nicotine content [0.28, 0.10] and VLNC [0.06] mg yield) on abstinence-induced craving and withdrawal, affect, perceptions of risk, product acceptability and demand for usual-brand cigarettes in adolescent smokers across four laboratory sessions (n=78). In Study 2 we will randomize adolescent daily smokers (n = 90) to either receive VLNC cigarettes or normal-nicotine content (NNC; 0.83 mg) study cigarettes for three weeks. Participants will be instructed to smoke only those cigarettes. We will conduct daily assessments of total cigarette use (both study cigarette and non-compliant use of usual brand cigarettes; these daily data will be monitored closely for evidence of compensatory smoking), craving, and withdrawal, weekly assessments of breath CO levels, cigarette acceptability, risk perceptions of VLNC and NNC cigarettes and demand for usual-brand cigarettes, and pre- vs. post-use measures of nicotine and toxicant exposure (cotinine and NNAL). Overall, the project will help determine how VLNC cigarettes may affect real-world smoking behavior in adolescents, and illuminate the potential mechanisms through which these products may effect such changes. Such knowledge will contribute to the science base that may inform future policy decisions, and the future grant applications that will be generated from this line of research will ensure that the Candidate experiences a successful transition to becoming an independent researcher. Overall, the research and training activities outlined in this K01 award contribute both to an important area of scientific inquiry, and to the development of a productive and independent research career for the Candidate.